Black Women's Health Study Research Articles

Mammographic density and breast cancer risk among Black American women.

High mammographic density is a well-established risk factor for breast cancer; however, data from Black women are limited. It is largely unknown how mammographic density is associated with breast cancer subtypes among Black women. We examined the association between percent mammographic density (PMD) and breast cancer risk among participants in the Black Women's Health Study. Digital screening mammograms were available for 363 cases and 5541 non-cases. Cumulus software was used to assess PMD. We used inverse probability of sampling weights and Cox proportional hazards models, adjusted for age and body mass index, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) overall and by age at mammography and estrogen receptor (ER) status of the breast tumors. Multivariable models included additional breast cancer risk factors. Tests of statistical significance were 2-sided. In simple models, women in the highest quartile of PMD had 53% increased odds of breast cancer compared to those in the lowest quartile (HR 1.53; 95% CI: 1.11, 2.11). HRs were 1.37 (95% CI: 0.83, 2.24) among women <55 years of age and 1.68 (95% CI: 1.10, 2.56) among women aged ≥55 years. HRs were 1.49 (95% CI: 1.02, 2.16) for ER+ cancer and 1.45 (95% CI: 0.73, 2.87) for ER- cancer. Associations were largely unchanged in multivariable models. In this study of U.S. Black women, higher PMD was associated with ER+ and ER- breast cancer risk. Findings from this study reinforce the importance of breast density as a risk factor for breast cancer in Black women.

Clinical, Diagnostic, and Metabolic Characteristics Associated with Nephrolithiasis in the Black Women's Health Study.

Background/Objectives: Nephrolithiasis (kidney stones) is a frequently occurring urologic condition resulting in significant patient morbidity and healthcare costs. Despite the higher prevalence of metabolic risk factors for nephrolithiasis among Black women, there have been few epidemiologic studies of kidney stones focusing on this group. Methods: We describe demographic and health characteristics, diagnostics, and metabolic profiles of US Black women with self-reported kidney stones. The women were participants in the Black Women's Health Study (BWHS), a large prospective cohort of US Black women (median age 38 years) begun in 1995. Results: Among the 2750 BWHS participants who completed an online supplemental questionnaire assessing urologic health, 201 women reported nephrolithiasis. Of this number, 62% had completed ≥ 16 years of education, and 82% reported access to health care. Overall, 39% reported experiencing ≥ 2 stones in their lifetime, and 29% required surgery to treat the condition. Thirty-two percent reported having completed a metabolic evaluation, while 70% had undergone a CT scan to diagnose nephrolithiasis. The frequency of metabolic evaluation increased with the number of metabolic components reported: 3% (0 components) to 43% (3-4 components). Conclusions: Our findings are consistent with reports of lower rates of metabolic evaluation among Black patients despite their having multiple risk factors for nephrolithiasis. Further study is needed to identify the barriers and facilitators of metabolic and diagnostic workup of nephrolithiasis in Black women.

Lifecourse growth and development determinants of mammographic density in Black women.

High mammographic density is one of the strongest breast cancer risk factors; however, determinants of high mammographic density are understudied in Black women. We assessed growth and development factors across the lifecourse in relation to mammographic density. Within the Black Women's Health Study (BWHS), we used Cumulus software to assess percent mammographic density from digital screening mammograms for 5,905 women ages 40-74. We fit linear regression models to quantify the association of lifecourse characteristics including birth weight, childhood somatotype, age at menarche, body mass index (BMI) at age 18, height, BMI at mammography, and adulthood waist-to-hip ratio with density overall and by age. We also performed a path analysis to assess the total and mediating effects of the growth and development factors on density. BMI at age 18, height, BMI at mammography, and waist-to-hip ratio were significantly and inversely associated with density. On path analysis, total effects of childhood somatotype (standardized  = -0.05, p <0.001), BMI at age 18 (standardized  = -0.13, p <0.001), BMI at mammography (standardized  = -0.22, p <0.001), and waist-to-hip ratio (standardized  = -0.04, p <0.001) were associated with density. Several factors across the lifecourse - greater childhood somatotype, BMI at age 18, height, BMI at mammography, and waist-to-hip ratio - were associated with lower mammographic density in this cohort of Black women. Body size closer to the time of mammography may be more meaningful in determining mammographic density, though early life adiposity also influences mammographic density.

Pack-Year Smoking History: An Inadequate and Biased Measure to Determine Lung Cancer Screening Eligibility.

Pack-year smoking history is an imperfect and biased measure of cumulative tobacco exposure. The use of pack-year smoking history to determine lung cancer screening eligibility in the current US Preventive Services Task Force (USPSTF) guideline may unintentionally exclude many high-risk individuals, especially those from racial and ethnic minority groups. It is unclear whether using a smoking duration cutoff instead of a smoking pack-year cutoff would improve the selection of individuals for screening. We analyzed 49,703 individuals with a smoking history from the Southern Community Cohort Study (SCCS) and 22,126 individuals with a smoking history from the Black Women's Health Study (BWHS) to assess eligibility for screening under the USPSTF guideline versus a proposed guideline that replaces the ≥20-pack-year criterion with a ≥20-year smoking duration criterion. Under the USPSTF guideline, only 57.6% of Black patients with lung cancer in the SCCS would have qualified for screening, whereas a significantly higher percentage of White patients with lung cancer (74.0%) would have qualified (P < .001). Under the proposed guideline, the percentage of Black and White patients with lung cancer who would have qualified for screening increased to 85.3% and 82.0%, respectively, eradicating the disparity in screening eligibility between the groups. In the BWHS, using a 20-year smoking duration cutoff instead of a 20-pack-year cutoff increased the percentage of Black women with lung cancer who would have qualified for screening from 42.5% to 63.8%. Use of a 20-year smoking duration cutoff instead of a 20-pack-year cutoff greatly increases the proportion of patients with lung cancer who would qualify for screening and eliminates the racial disparity in screening eligibility between Black versus White individuals; smoking duration has the added benefit of being easier to calculate and being a more precise assessment of smoking exposure compared with pack-year smoking history.

Perceived Experiences of racism in Relation to Genome-Wide DNA Methylation and Epigenetic Aging in the Black Women's Health Study.

African American women have a disproportionate burden of disease compared to US non-Hispanic white women. Exposure to psychosocial stressors may contribute to these health disparities. Racial discrimination, a major stressor for African American women, could affect health through epigenetic mechanisms. We conducted an epigenome-wide association study (EWAS) to examine the association of interpersonal racism (in daily life and in institutional settings) with DNA methylation in blood in 384 participants of the Black Women's Health Study (BWHS). We also evaluated whether a greater number of perceived experiences of racism was associated with epigenetic aging as measured using different methylation clocks. Models were adjusted for chronological age, body mass index, years of education, neighborhood SES, geographic region of residence, alcohol drinking, smoking, and technical covariates. Higher scores of racism in daily life were associated with higher methylation levels at the cg04494873 site in chromosome 5 (β = 0.64%; 95% CI = 0.41%, 0.87%; P = 6.35E-08). We also replicated one CpG site, cg03317714, which was inversely associated with racial discrimination in a previous EWAS among African American women. In the BWHS, higher scores of racism in daily life were associated with lower methylation levels at that CpG site (β = -0.94%; 95% CI = -1.37%, -0.51%; P =2.2E-05). Higher racism scores were associated with accelerated epigenetic aging in more than one methylation clock. Exposure to discriminatory events may affect the epigenome and accelerate biological aging, which may explain in part the earlier onset of disease in African American women.

Perceived Interpersonal Racism in Relation to Incident Coronary Heart Disease Among Black Women.

Racism is highly prevalent in the United States. Few data exist about whether perceived interpersonal racism is associated with risk of coronary heart disease (CHD). We followed 48 305 participants in the Black Women's Health Study through biennial mailed and Internet-based health questionnaires from 1997, when they provided information on perceived interpersonal racism and were free of cardiovascular disease and cancer, until the end of 2019. We averaged participant responses to 5 validated questions about perceived interpersonal racism in everyday activities, such as "people act as if they think you are dishonest." We summed the positive responses to 3 questions about perceived racism in interactions that involved jobs, housing, and police; scores ranged from 0 (no to all) to 3 (yes to all). CHD cases were defined as nonfatal myocardial infarctions confirmed through medical records, fatal cases identified through the National Death Index, and self-reported revascularization events. We used Cox proportional hazard models adjusting for major confounders to estimate hazard ratios (HRs). During 22 years of follow-up, we identified 1947 incident CHD cases. For women who reported experiences of racism in employment, housing, or involving the police relative to women who reported no such experiences, the age-adjusted HR for CHD was 1.35 (95% CI, 1.13-1.61; Ptrend=0.006), and the multivariable HR for CHD was 1.26 (95% CI, 1.05-1.51; Ptrend=0.05). For women in the highest quartile of perceived interpersonal racism in daily life relative to women in the lowest quartile, the age-adjusted HR for CHD was 1.25 (95% CI, 1.07-1.46; Ptrend=0.006). After multivariable adjustment, the HR was attenuated and no longer statistically significant. Perceived experiences of interpersonal racism in employment, in housing, and with the police were associated with higher incidence of CHD among Black women, whereas perceived racism in everyday life was not associated with higher risk.

Body size and risk of multiple myeloma in the Black Women's Health Study.

Obesity is an established risk factor for multiple myeloma (MM). Relatively few prior studies, however, have evaluated associations in Black populations. Among 55,276 participants in the Black Women's Health Study, a prospective U.S. cohort established in 1995, we confirmed 292 incident diagnoses of MM over 26 years of follow-up. Multivariable Cox proportional hazard models, adjusted for age and putative MM risk factors, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of usual body mass index (BMI), BMI at age 18, height, and waist-to-hip ratio with MM. Compared to women with a usual adult BMI < 25 kg/m2, the HR associated with a usual adult BMI ≥ 35 kg/m2 was 1.38 (95% CI: 0.96, 1.98). For early adult BMI, the HR comparing women with BMI ≥ 25 vs. <25 kg/m2 was 1.57 (95% CI: 1.08, 2.28). Women who were heavy in both early and later life had the highest risk compared to those who were lean at both time points (HR: 1.60; 95% CI: 1.02, 2.52). Height was also associated with the risk of MM; the HR per 10 cm was 1.21 (95% CI: 1.02, 1.43). These results indicate that high early adult BMI is associated with a 57% increased risk of MM in Black women and potentially highlight the importance of weight control as a preventive measure.

Psychosocial stressors and breast cancer gene expression in the Black Women's Health Study.

Prior studies indicate that the physiologic response to stress can affect gene expression. We evaluated differential gene expression in breast cancers collected from Black women with high versus low exposure to psychosocial stressors. We analyzed tumor RNA sequencing data from 417 Black Women's Health Study breast cancer cases with data on early life trauma and neighborhood disadvantage. We conducted age-adjusted differential gene expression analyses and pathway analyses. We also evaluated Conserved Transcriptional Response to Adversity (CTRA) contrast scores, relative fractions of immune cell types, T cell exhaustion, and adrenergic signaling. Analyses were run separately for estrogen receptor positive (ER+; n = 299) and ER- (n = 118) cases. Among ER+ cases, the top differentially expressed pathways by stress exposure were related to RNA and protein metabolism. Among ER- cases, they were related to developmental biology, signal transduction, metabolism, and the immune system. Targeted analyses indicated greater immune pathway enrichment with stress exposure for ER- cases, and possible relevance of adrenergic signaling for ER+ cases. CTRA contrast scores did not differ by stress exposure, but in analyses of the CTRA components, ER- breast cancer cases with high neighborhood disadvantage had higher pro-inflammatory gene expression (p = 0.039) and higher antibody gene expression (p = 0.006) compared to those with low neighborhood disadvantage. There are multiple pathways through which psychosocial stress exposure may influence breast tumor biology. Given the present findings on inflammation and immune response in ER- tumors, further research to identify stress-induced changes in the etiology and progression of ER- breast cancer is warranted.

Abstract B145: Validation of a colorectal cancer risk prediction model in US Black women

Abstract Background: The National Cancer Institute’s Colorectal Cancer Risk Assessment Tool (NCI-CCRAT) estimates an individual's five-year risk of developing colorectal cancer. It was developed by estimating relative risks from a population of US White women and men and incorporating race, gender, and age-specific incidence data from population-based cancer registries. However, the model performance has not been assessed for Black Americans, who have the highest colorectal cancer incidence and mortality rates of any US racial/ethnic group. Methods: The NCI-CCRAT estimates the absolute risk of colorectal cancer based on an individual’s age, sex, family history of colorectal cancer, sigmoidoscopy/colonoscopy, polyps, smoking, physical activity, regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use, vegetable intake, body mass index, and hormone replacement therapy use. Validation of the NCI-CCRAT was performed using prospective data from 57,558 participants ages 40 to 84 years in the Black Women's Health Study (BWHS). We predicted 5-year absolute risk using data from 2001 through 2015 in three 5-year prediction periods: 2001-2005, 2006-2010, and 2011-2015. To assess model performance, we computed calibration by comparing the expected number of colorectal cancer cases predicted by the model to the observed number of cases (E/O) in the BWHS overall and in subgroups of the population. We assessed discriminatory accuracy by calculating the area under the curve (AUC). Results: During follow-up from 2001 through 2015 (634,512 person-years), 433 BWHS participants developed invasive colorectal cancer. Based on the NCI-CCRAT, 543 cases were expected. The NCI-CCRAT was well-calibrated in the first 5-year prediction period (2001-2005 E/O=1.03, 95% CI: 0.88–1.21), but the model overestimated risk in the subsequent 5-year prediction periods, with E/O=1.30 for 2006-2010 and E/O=1.44 for 2011-2015. The overall E/O ratio was 1.25 (95% confidence interval: 1.14–1.38), indicating that NCI-CCRAT overestimated the number of cases in this population of Black women. Of note, associations with colorectal cancer were weaker in the BWHS than in the development cohort for vigorous physical activity, aspirin/NSAID use, vegetable intake, and body mass index. We estimated discriminatory accuracy only for the first 5-year prediction period (2001-2005, N cases=151) for which the model was well calibrated, and obtained an age-adjusted AUC of 0.61 (95% CI: 0.57–0.66). Conclusions: The NCI-CCRAT overestimated the overall number of colorectal cancer cases by 25% in this prospective cohort of Black women, possibly due to population-specific differences in the relative risks of key factors driving colorectal cancer incidence. Discriminatory accuracy was similar to measures from the original validation cohort of White women and men. Impact: This study suggests that further research is needed to determine the most important predictors of colorectal cancer etiology in Black women and to develop and test a colorectal cancer risk prediction model for Black Americans. Citation Format: Jessica L. Petrick, Nelsy Castro-Webb, Gary R. Zirpoli, Kerrie P. Nelson, Julie R. Palmer, Ruth M. Pfeiffer. Validation of a colorectal cancer risk prediction model in US Black women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B145.

Hair relaxer use and risk of uterine cancer in the Black Women's Health Study

BackgroundChemical hair relaxers, use of which is highly prevalent among Black women in the US, have been inconsistently linked to risk of estrogen-dependent cancers, such as breast cancer, and other reproductive health conditions. Whether hair relaxer use increases risk of uterine cancer is unknown. MethodsIn the Black Women's Health Study, 44,798 women with an intact uterus who self-identified as Black were followed from 1997, when chemical hair relaxer use was queried, until 2019. Over follow-up, 347 incident uterine cancers were diagnosed. We used multivariable Cox proportional hazards regression models, adjusted for age and other potential confounders, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of hair relaxer use with risk of uterine cancer. ResultsCompared to women who never used hair relaxers or used them infrequently (<4 years and ≤1–2 times/year), the HR for uterine cancer associated with heavy use (≥15 years and at least 5 times/year) was 1.18 (95% CI: 0.81, 1.71). However, among postmenopausal women, compared to never/light use, the HR for moderate use was 1.60 (95% CI: 1.01, 2.53), the HR for heavy use was 1.64 (1.01, 2.64), and the HR for ≥20 years of use regardless of frequency was 1.71 (1.08, 2.72). Results among premenopausal women were null. ConclusionsIn this large cohort of Black women, long-term use of chemical hair relaxers was associated with increased risk of uterine cancer among postmenopausal women, but not among premenopausal women. These findings suggest that hair relaxer use may be a potentially modifiable risk factor for uterine cancer.

Vitamin D and monoclonal gammopathy of undetermined significance (MGUS) among U.S. Black women.

Risk factors for monoclonal gammopathy of undetermined significance (MGUS), the asymptomatic precursor to multiple myeloma, are largely unknown. We hypothesized that low vitamin D levels might be associated with higher MGUS prevalence in a national cohort of U.S. Black women. We screened archived serum samples (collected 2014-2017) from 3896 randomly selected participants in the Black Women's Health Study ages 50-79 for evidence of MGUS; samples had been assayed for 25-hydroxyvitamin D [25(OH)D] shortly after blood draw. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between 25(OH)D level and MGUS status, adjusting for age, body mass index, and season of blood draw. We identified 334 MGUS cases (8.6%) in the study population. The adjusted OR comparing women with vitamin D deficiency (25(OH)D < 20 ng/mL) to those with 25(OH)D levels ≥ 30 ng/mL was 1.27 (95% CI: 0.95, 1.72). MGUS was more prevalent among Black women with vitamin D deficiency compared to those with 25(OH)D ≥ 30 ng/mL; however, the association was not statistically significant. Future prospective studies are warranted to clarify the possible association between vitamin D and MGUS.

Validating a model for predicting breast cancer and nonbreast cancer death in women aged 55 years and older.

To support mammography screening decision making, we developed a competing-risk model to estimate 5-year breast cancer risk and 10-year nonbreast cancer death for women aged 55 years and older using Nurses' Health Study data and examined model performance in the Black Women's Health Study (BWHS). Here, we examine model performance in predicting 10-year outcomes in the BWHS, Women's Health Initiative-Extension Study (WHI-ES), and Multiethnic Cohort (MEC) and compare model performance to existing breast cancer prediction models. We used competing-risk regression and Royston and Altman methods for validating survival models to calculate our model's calibration and discrimination (C index) in BWHS (n = 17 380), WHI-ES (n = 106 894), and MEC (n = 49 668). The Nurses' Health Study development cohort (n = 48 102) regression coefficients were applied to the validation cohorts. We compared our model's performance with breast cancer risk assessment tool (Gail) and International Breast Cancer Intervention Study (IBIS) models by computing breast cancer risk estimates and C statistics. When predicting 10-year breast cancer risk, our model's C index was 0.569 in BWHS, 0.572 in WHI-ES, and 0.576 in MEC. The Gail model's C statistic was 0.554 in BWHS, 0.564 in WHI-ES, and 0.551 in MEC; IBIS's C statistic was 0.547 in BWHS, 0.552 in WHI-ES, and 0.562 in MEC. The Gail model underpredicted breast cancer risk in WHI-ES; IBIS underpredicted breast cancer risk in WHI-ES and in MEC but overpredicted breast cancer risk in BWHS. Our model calibrated well. Our model's C index for predicting 10-year nonbreast cancer death was 0.760 in WHI-ES and 0.763 in MEC. Our competing-risk model performs as well as existing breast cancer prediction models in diverse cohorts and predicts nonbreast cancer death. We are developing a website to disseminate our model.

Aspirin and nonaspirin nonsteroidal antiinflammatory drug use and occurrence of colorectal adenoma in Black American women.

Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self-identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow-up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between aspirin use and colorectal adenoma among 34 397 women who reported at least 1 colonoscopy or sigmoidoscopy. From 1997 through 2018, 1913 women were diagnosed with an adenoma. Compared to nonaspirin users, regular users had 14% (OR = 0.86, 95% CI: 0.78-0.95) lower odds of adenoma. The odds of adenoma decreased with increasing duration of aspirin use (≥10 years: OR = 0.80, 95% CI: 0.66-0.96). Initiating aspirin at a younger age was associated with a reduced adenoma occurrence (age < 40 years at initiation: OR = 0.69, 95% CI: 0.55-0.86). Regular aspirin use was associated with a decreased odds of colorectal adenoma in our study of Black women. These findings support evidence demonstrating a chemopreventive impact of aspirin on colorectal neoplasia and suggest that aspirin may be a useful prevention strategy among US Black women.

Ethical, legal, and social implications (ELSI) and challenges in the design of a randomized controlled trial to test the online return of cancer genetic research results to U.S. Black women

BackgroundA central challenge to precision medicine research efforts is the return of genetic research results in a manner that is effective, ethical, and efficient. Formal tests of alternate modalities are needed, particularly for racially marginalized populations that have historically been underserved in this context. MethodsWe are conducting a randomized controlled trial (RCT) to test scalable modalities for results return and to examine the clinical utility of returning genetic research results to a research cohort of Black women. The primary aim is to compare the efficacy of two communication modalities for results return: 1) a conventional modality that entails telephone disclosure by a Board-certified genetic counselor, and 2) an online self-guided modality that entails results return directly to participants, with optional genetic counselor follow-up via telephone. The trial is being conducted among participants in the Black Women's Health Study (BWHS), where targeted sequencing of 4000 participants was previously completed. ResultsSeveral ethical, legal, and social implications (ELSI) and challenges presented, which necessitated substantial revision of the original study protocol. Challenges included chain of custody, re-testing of research results in a CLIA lab, exclusion of VUS results, and digital literacy. Bioethical principles of autonomy, justice, non-maleficence, and beneficence were considered in the design of the study protocol. ConclusionThis study is uniquely situated to provide critical evidence on the effectiveness of alternative models for genetic results return and provide further insight into the factors influencing access and uptake of genetic information among U.S. Black women.Clinicaltrials.gov: NCT04407611

Perceived racism associated with declines in self-rated oral health among U.S. Black women

Racial disparities in oral health are well-documented. Stress has been associated with both perceived racism and oral health, yet little research has directly investigated the association between perceived racism and oral health. We used data from the Black Women's Health Study, a longitudinal cohort study that includes a geographically diverse sample of Black women across the United States. Perceived exposure to racism was assessed via two scales, one assessing lifetime exposure and one everyday exposure. Self-rated oral health was subsequently assessed over multiple time points. We used Cox proportional hazard models to calculate adjusted incidence rate ratios estimating the association between higher levels of perceived racism and incident "fair" or "poor" oral health, and explored potential effect measure modification using stratified models. The adjusted incidence rate ratios (n=27,008) relating perceived racism to incident fair or poor oral health were 1.50 (95% confidence interval 1.35, 1.66) comparing the highest quartile of everyday racism to the lowest and 1.45 (95% confidence interval 1.31, 1.61) for the highest score of lifetime racism compared to the lowest. We did not see evidence of effect modification. Higher levels of perceived racism documented in 2009 were associated with declines in self-rated oral health from 2011 to 2019.

Abstract 3007: Psychosocial stressors and breast cancer gene expression in the Black Women's Health Study

Abstract Introduction: Chronic sympathetic nervous system (SNS) activation following exposure to psychosocial stressors may influence cancer risk through dysregulation of immune function or adrenergic signaling pathways. Prior research out of the Black Women’s Health Study (BWHS) reported associations between psychosocial stressors and breast cancer risk. We hypothesized that women with greater exposure to psychosocial stressors before their breast cancer diagnosis have higher tumor gene expression of immune-related and adrenergic signaling pathways. Methods: The BWHS is a large, prospective cohort study that has collected health and lifestyle information biennially since 1995. We included data from 417 BWHS breast cancer cases with RNA sequencing data and information on early-life trauma and neighborhood disadvantage. We used the R package DESeq2 to conduct age-adjusted differential gene expression analyses by levels of each stress exposure and described the top differentially expressed pathways using the Molecular Signature Database REACTOME subset of canonical pathways. Targeted analyses of immune-related pathways used CIBERSORT to quantify the proportions of infiltrating immune cells and the R package GSVA for single-sample gene set enrichment analysis (ssGSEA) of genes comprising a T cell exhaustion signature. We also used ssGSEA to evaluate a set of genes involved in adrenergic signaling. Given the variability in gene expression for ER+ versus ER- breast cancers, all analyses were run separately for ER+ (n=299) and ER- (n=118) tumors. Results: Pathways related to nervous system development and the metabolism of RNA were differentially expressed by levels of stress exposures among ER+ and ER- cases, while pathways related to immune function and adrenergic signaling were differentially expressed only among ER- cases, and only when evaluating differential gene expression by levels of neighborhood disadvantage. Targeted analyses of tumor immune infiltration showed significantly higher B cell fractions among ER+ cases without exposure to early trauma compared to those with early trauma. The relative fractions of other immune cells did not differ by stress exposure for ER+ or ER- tumors. Findings from ssGSEA gene set analyses indicated similar expression of genes involved in T cell exhaustion and adrenergic signaling pathways by stress exposure levels for both ER+ and ER- breast cancers. Conclusions: Our findings provide evidence of differential gene expression by levels of stress exposure; however, the differential expression may be driven by multiple pathways and not just the hypothesized immune-related and adrenergic signaling pathways. Additional studies are needed to describe mechanisms by which psychosocial stressors may influence breast cancer risk, both overall and by gene expression profile. Citation Format: Mollie E. Barnard, Xutao Wang, Jessica L. Petrick, W. Evan Johnson, Julie R. Palmer. Psychosocial stressors and breast cancer gene expression in the Black Women's Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3007.

Epidemiology of Inflammatory Bowel Disease in a Cohort of US Black Women.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, are inflammatory diseases of the gastrointestinal tract. The incidence of IBD is increasing in minority populations; however, little is known about the epidemiology and disease characteristics of IBD in Black women. Our study population included participants in the Black Women's Health Study. Diagnosis of IBD was self-reported through the biennial questionnaires starting at baseline in 1995. We estimated the incidence of IBD according to age and geographic region. A follow-up supplementary questionnaire was also sent to a subset of participants who reported diagnosis of IBD to evaluate the accuracy of self-reported diagnosis and to assess disease characteristics. Through December 31, 2021, a total of 609 cases of IBD were reported, of which 142 were prevalent at baseline (prevalence, 0.24%), and 467 were incident (crude incidence rate, 33.2/100 000 person-years). The incidence of IBD was highest in the younger than 30 years age group and similar across geographic region. Among the participants who responded to the supplementary questionnaire, 57.1% had confirmed diagnosis of IBD. In a large prospective cohort of US Black women, we found that the incidence of IBD was similar to previously published estimates in US White women. Future studies should focus on identifying risk factors for IBD in Black individuals in the United States.

Abstract P473: Early Onset Stroke in the Black Women's Health Study

Background: The impact of stroke in young adulthood and mid-life is disproportionately large due to greater disability-adjusted life-years lost and worsened quality of life. There is evidence that stroke incidence has increased among young adults in recent decades, although there is conflicting data, especially among subgroups defined by sex and race. We investigated incidence of early-onset stroke among U.S. Black women. Methods: The Black Women’s Health Study is a prospective study of 59,000 Black women from across the U.S. who have been followed since 1995 (aged 21-69 years, median age of 38 years). Both ischemic and hemorrhagic stroke were ascertained by self-report at biennial health questionnaires through December 31, 2019. Stroke mortality was determined through the National Death Index. We stratified by age group: ages 35-54 and ages 55 and older, to distinguish early onset stroke and stroke occurring in later life. We examined crude incidence rates of total stroke cases (per 1000 person-years) during two sequential 12-year follow up periods, 1995-2007 and 2007-2019. Stroke incidence rates were calculated and modeled with Poisson regression. Results: Incident stroke or stroke death occurred in 2093/58,386 participants (3.58%) during 1,316,545 person-years of follow-up from 1995 to 2019. Among women aged 35-54 years the incidence rate was 1.59 (95% CI 1.46-1.72) in the 1995-2007 period (564 cases/355,601 person-years) and 1.12 (95% CI 1.02-1.23) in the 2007-2019 period (460 cases/409,870 person-years). For participants aged 55 or older the incidence rate was 4.19 (95% CI 3.69-4.73) in the 1995-2007 period (257 cases/61,357 person-years) and 2.83 (95% CI 2.62-3.05) in the 2007-2019 period (678 cases/239,433 person-years). Conclusion: In this preliminary analysis, stroke incidence in Black women decreased across study time periods, from 1995-2019, most clearly among participants aged 55 years or older. These findings are similar to those observed in other population-based cohorts reporting incidence rates among Black Americans, for example in the Atherosclerosis Risk in Communities Study. Black women continue to be a high-risk subgroup for stroke and should be a focus for preventive public health efforts, from as early as young adulthood.

Correlates of nephrolithiasis in US black women: data from the black women’s health study

Nephrolithiasis is a common urologic condition and a significant source of patient morbidity and healthcare expenditure. There are few epidemiologic studies of kidney stones focusing exclusively on Black women. We retrospectively assessed the prevalence and correlates of self-reported kidney stones within the Black Women's Health Study (BWHS). Descriptive statistics and multivariable logistic regression models were used to explore factors associated with nephrolithiasis. As of the 2005 follow-up questionnaire, a cumulative total of 1063 women among 43,178 reported ever being diagnosed with kidney stones for a prevalence of 2.64%. Women with a history of nephrolithiasis were older, slightly heavier, and were more likely to have a comorbid condition (e.g., type-2 diabetes, gallstones), drink alcohol, and consume a Western-style diet. A history of gallstone disease was associated with an odds ratio (OR) of 3.59 (95% confidence interval (CI) 3.09-4.17). The OR for consuming ≥ 7 alcoholic beverages/week, compared to none was 0.61 (0.39-0.94), while the OR for high adherence to the Western diet, compared to low adherence was 1.53 (1.23-1.90). Our findings are consistent with previous studies of primarily white populations relating lifestyle-associated risk factors with nephrolithiasis. Despite their lower prevalence of kidney stones, it is important to focus on vulnerable populations such as Black women given their disproportionate burden of metabolic conditions (e.g., obesity, diabetes) related to kidney stone disease.

Vitamin D and risk of hypertension among Black women.

Evidence of an association between plasma 25-hydroxyvitamin D [25(OH)D] levels and risk of hypertension, predominantly from studies of White individuals, suggests an inverse relationship. Limited data are available on Black individuals, who are more likely to have vitamin D deficiency. In the Black Women's Health Study (BWHS), a prospective study of 59 000 self-identified Black women from across the US, we assessed levels of a validated predicted vitamin D score in relation to incident hypertension. We followed 42 239 participants who were free of cardiovascular disease and cancer from 1995 to 2019, during which time 19 505 incident cases of hypertension were identified. Cox proportional hazards model were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of predicted vitamin D with the risk of incident hypertension. In age-adjusted analyses, there was a strong inverse dose-response association between predicted vitamin D score and hypertension risk, with an HR of .66 (95% CI: .63-.68, p trend<.0001) for the highest quartile of predicted vitamin D relative to the lowest. After control for potential confounders including body mass index, physical activity, and cigarette smoking, the HR was attenuated to .91 (95% CI: .87-.95, p trend=.002). In this prospective cohort study of Black women, predicted vitamin D score was weakly inversely associated with the incidence of hypertension. This observed association may reflect an inability to fully control for confounding factors.